Efficacy of Ketoprofen With or Without Omeprazole for Pain And Inflammation Control After Third Molar Removal - SciELO
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Brazilian Dental Journal (2018) 29(2): 140-149
ISSN 0103-6440
http://dx.doi.org/10.1590/0103-6440201802254
Efficacy of Ketoprofen With or Without
1Department of Biological
Sciences, Bauru School of
Dentistry, USP - Universidade de
Omeprazole for Pain And Inflammation São Paulo, Bauru, SP, Brazil
2Department of Pediatric Dentistry,
Control After Third Molar Removal Orthodontics and Community
Health, Bauru School of Dentistry,
USP - Universidade de São
Paulo, Bauru, SP, Brazil
Luis Fernando Simoneti1, Giovana Maria Weckwerth1, Thiago José Dionísio1,
Elza Araujo Torres1, Paulo Zupelari-Gonçalves1, Adriana Maria Calvo1, José Correspondence: Carlos F. Santos,
Roberto Lauris2, Flávio Cardoso Faria1, Carlos Ferreira Santos1 Alameda Octávio Pinheiro Brisolla,
975, 17012-901. Bauru, SP, Brazil.
Phone/Fax: +55 14 32358295.
e-mail: cfsantos@fob.usp.br
In view of the gastrointestinal problems generated by the ketoprofen use, the ketoprofen
association with omeprazole is available on the market. However, this association efficacy
in acute pain control has not been established. Bilateral extraction of lower third molars
in similar positions is currently the most used model for the evaluation and investigation
of the efficacy and pharmacological effects of new compounds for the treatment of acute
postoperative pain. The randomized and crossover study consisted in evaluating the clinical
efficacy of therapy performed by ketoprofen 100 mg (twice daily–b.i.d.) versus ketoprofen
200 mg + omeprazole 20 mg (once daily-q.d.) to pain, swelling and trismus control in
the bilateral extraction model of lower third molars in similar positions in two different
appointments, in 50 volunteers. Volunteers reported significantly less postoperative
pain at various post-operative periods and consumed less rescue analgesic medication
(acetaminophen 750 mg) throughout the study when they took the combination of
ketoprofen 200 mg + omeprazole 20 mg (q.d.). Following administration of both study
drugs, no gastrointestinal adverse reactions were reported by volunteers. Furthermore,
the evaluations of the drugs in pain control by the volunteers were significantly favorable
to ketoprofen 200 mg + omeprazole 20 mg (q.d.). For swelling and trismus control, the
treatments presented similar results. In conclusion, when volunteers took ketoprofen
200 mg + omeprazole 20 mg (q.d.), they reported significantly less postoperative pain at Keywords: ketoprofen,
various post-surgical periods and consumed less rescue analgesic medication throughout omeprazole, pain control,
the study compared with ketoprofen 100 mg (b.i.d). lower third molar surgery.
Introduction of limitation of mouth opening is expected.
Bilateral extraction of lower third molars in similar To prevent the occurrence of postoperative
positions is currently the most used model for the evaluation complications, such as acute pain, studies indicate the
and investigation of the efficacy and pharmacological use of physical procedures, such as the use of cold packs
effects of new compounds for the treatment of postoperative soon after the surgeries. In addition to these procedures,
pain, such as analgesics and anti-inflammatory drugs (1,2). non-steroidal anti-inflammatory drugs (NSAIDs) have been
This type of surgical procedure is recommended since some extensively used as adjuvants for the reduction of these
tissues are manipulated and traumatized in the region postoperative complications derived from the extractions
where the extraction is performed, composed mainly of of the lower third molars (1,2,8,9).
loose connective tissue that contains blood and lymphatic Scientific evidence demonstrates that NSAIDs exhibit
vessels. Due to their manipulation, a number of functional their therapeutic effect by inhibiting cyclooxygenase
and structural changes are expected; among them are the (COX), and this inhibits the production of prostaglandins
release of exudate and the formation of swelling, with (PGs) and thromboxanes. According to the literature, PGs
subsequent onset of trismus and pain (3-5). alone do not cause pain, but they potentiate the action of
Pain resulting from the extraction of third molars is chemical mediators of inflammation, such as bradykinin
usually short in duration and of moderate intensity, with on the nociceptive fibers, which consequently cause pain
greater pain intensity soon after the surgical procedure amplification (10). COX is known in two isoforms: COX-1,
(6). Swelling is formed due to tissue manipulation during and COX-2. A third isoform of this enzyme family, known as
surgery, and presents maximum intensity after 48 h of the COX-3 has been discovered, which unlike COX-1 and COX-
surgical procedure (7). Trismus after third molar extraction 2, would not produce proinflammatory prostanoids, but
is closely related to the level of swelling and inflammation rather anti-inflammatory substances. COX-1 is known as a
generated by the surgery, ie, the greater the level of swelling constitutive enzyme. It is associated with the production of
resulting from an inflammatory response, the greater degree prostaglandins and results in several physiological effects,Braz Dent J 29(2) 2018
such as gastric protection, platelet aggregation, vascular mg tablets (b.i.d.) versus ketoprofen 200 mg + omeprazole
homeostasis and maintenance of renal blood flow (11). 20 mg (q.d.), both administered enterally for the control
NSAIDs are commonly prescribed to combat a of pain, swelling and trismus in the bilateral extraction
wide variety of inflammatory pain conditions such as model of lower third molars with similar positions in two
osteoarthritis, rheumatic diseases, soft tissue trauma, and different appointments.
postoperative pain. NSAIDs are also commonly used in
dental practice, such as in the treatment of orofacial pain Material and Methods
or pain after surgical procedures such as dental extractions The present randomized and cross-over study was
(1,2,8,9). Ketoprofen is a non-steroidal anti-inflammatory performed in volunteers regularly enrolled at the Bauru
drug, derived from arylcarboxylic acid, belonging to the School of Dentistry, University of São Paulo, after
propionic acid group of NSAIDs. Ketoprofen has anti- approval by the Institutional Review Board (CAAE:
inflammatory, antipyretic and peripheral and central 44808215.6.0000.5417) in accordance with the Declaration
analgesic activity. It inhibits the synthesis of prostaglandins of Helsinki for Human Research. The clinical trial was
and platelet aggregation, however, its mechanism of action registered under ID # NCT02730026 at ClinicalTrials.gov.
is not completely elucidated (10,12). Evidence from a The present study included healthy individuals (ASA I
number of clinical studies suggests that ketoprofen is an according to the classification of the American Society of
effective analgesic, with its therapeutic effect generally at Anesthesiologists) of both sexes, aged 18-38 years, with
doses ranging from 75 to 300 mg per day (12). Omeprazole is indication of bilateral third molar extraction.
a potent inhibitor of H+/K+ ATPase (proton pump inhibitor), Volunteers could not have inflammations or infections
which is responsible for the secretion of hydrochloric acid prior to surgical procedures, such as pericoronitis, alveolitis,
Ketoprofen with or without omeprazole for pain
by parietal gastric cells. Omeprazole was well established osteonecrosis or mucositis. In addition, the volunteers
as a highly effective inhibitor of acid secretion. The drug signed the Informed Consent Form. In order to standardize
has a long duration of action. Remaining acid secretion the sample, the volunteers should present the positions of
is significantly reduced at 21 days after withdrawal of the lower third molars, roots and similar degree of impaction
omeprazole 20 mg/day for 4 weeks in volunteers with on the right and left sides of the mouth according to the
duodenal ulcer. The effect of omeprazole on gastric acid classification of Pell and Gregory as well as Winter (16),
secretion is dose-dependent (13,14). which was confirmed by orthopantomographic radiography
In the international literature, several NSAIDs have been and clinical examination.
studied in randomized, cross-over models, demonstrating Eligibility criteria included adults without inflammation,
their efficacy in the management of acute pain after infection and systemic diseases that could possibly interfere
bilateral extraction of lower third molars in similar positions with the study. Exclusion criteria were as follows: any history
(1,2,8,9). This study model of bilateral removal of lower of allergy, gastrointestinal bleeding/ulcers, kidney disease,
third molars with similar positions is unique, since the asthma or any known allergic sensitivity to ketoprofen,
same surgery is essentially performed twice in the same omeprazole or any NSAID. Pregnant or lactating women
patient, and will serve as its own control, thus avoiding were also excluded from the study, as well as volunteers
response variations (10). who used antidepressants, diuretics or NSAIDs 7 days prior
In view of the gastrointestinal problems generated to the start of the experiments (1,2,8,9).
by the use of ketoprofen, the association of ketoprofen All lower third molars extractions were performed
with omeprazole is available on the market. However, the with the same technique and with the same magnitude
efficacy of this association in the acute control of pain has of surgical trauma, all third molars were impacted, with
not been established. In the combination of ketoprofen necessity of bone removal on both opposing sides of the
200 mg + omeprazole 20 mg the pharmacokinetic mandible in each of the volunteers of the research. All
profiles of the ketoprofen and omeprazole components surgeries were performed by the same oral & maxillofacial
are comparable to those of the separately administered surgeon (L.F.S.) and assisted by the same assistant in two
ketoprofen and omeprazole components, but the different appoints, being performed in two visits with
formulation has a sustained release form of ketoprofen intervals of one to two months. The choice of the side to be
and a gastroresistant release form of omeprazole, both operated on and the NSAID to be used [ketoprofen 100 mg
suitable for once-daily therapeutic dosing. There is no twice daily (b.i.d.) (Profenid®, Sanofi-Aventis Farmacêutica
influence on the pharmacokinetics of ketoprofen when Ltda, Suzano/SP, Brazil) or ketoprofen 200 mg + omeprazole
administered concomitantly with omeprazole, and vice 20 mg once daily (q.d.) (Profenid Protect®, Sanofi-Aventis
versa (15). Therefore, the objective of the present study Farmacêutica Ltda, Suzano/SP, Brazil), each hard gelatin
was to evaluate the clinical efficacy of ketoprofen 100 capsule contains 200 mg of ketoprofen (extended-release
141Braz Dent J 29(2) 2018
microgranules) and 20 mg of omeprazole (gastroresistant • Subjective evaluation of postoperative pain, which
microgranules) for 4 days] was done in a randomized was recorded by the volunteer himself on a Visual
manner using a randomization worksheet obtained through Analog Scale (0 to 100 mm). Subjective pain
the program available at: http://www.randomization.com, assessments were performed by volunteers at the
number 19482. following times after administration of the drugs
The randomization determined which side would be [0; 15; 30 and 45 min, 1; 1.5; 2; 3; 4; 5; 6; 7; 8;
operated and the drug to be prescribed in the first surgery. 10; 12; 16; 24, 48, 72 and 96 h];
Therefore, in the second surgery the opposite side would • Mouth opening (distance in mm between the
be operated and the other drug prescribed. The drugs edges of the upper and lower incisors during the
were coded in even and odd numbers and the only person maximum opening achieved by the volunteer)
responsible for prescribing the postoperative medication before the surgery, on the 2nd postoperative
knew which drug was being prescribed. This information day and at the time of sutures removal (7th day,
was not disclosed to researchers until the end of the study. respectively). The postoperative ability to open
All anesthetic procedures were performed with blockade the mouth was expressed as a percentage of the
of the buccal, lingual and inferior alveolar nerves, initially preoperative measurement;
administering a cartridge (1.8 mL) of local anesthetic. • Onset and duration of surgery after anesthetic
After anesthesia of the lower lip, half a cartridge (0.9 mL) administration;
of another tube not yet used and of the same anesthetic • Patients were asked if they experienced any
solution was administered by an infiltrative terminal discomfort and/or side effects at the time of
technique to diminish hemorrhage and guarantee mucosal appointment for suture removal;
anesthesia. The local anesthetic used was 4% articaine • Total amount of pain relief medication used
with 1:200,000 epinephrine, according to our laboratory (acetaminophen 750 mg);
studies (2,8,9,17,18). • Measurement of facial swelling on the 2nd
L. F. Simoneti et. al.
As a rescue analgesic medication, if the volunteer judged postoperative day and on the 7th postoperative
that the analgesia produced by the anti-inflammatory day (removal of stitches) and quality of healing.
drug provided was insufficient, acetaminophen (EMS S/A,
Hortolândia/SP, Brazil) was prescribed at 750 mg every 8 h Statistical Analysis
(2,8,9,17-20). Throughout the surgical procedure, notations G*Power software v.3.0.10 was used for the sample
were made such as: the amount of anesthetic administered, calculation. Data were tabulated using Microsoft® Excel
the hemodynamic data of the volunteer at each surgical 2012 (version 10.6871.6870) and GraphPad Prism (version
stage through the DX 2021 Dixtal device (Biomédica Ind e 4.0) was used to perform statistical analysis. For comparison
Com Ltda, Marília/SP, Brazil), the amount of bleeding and of some parameters proposed in the study the paired t test
the degree of difficulty of each stage of surgery (incision, for the parametric data and the Wilcoxon test for non-
flap, osteotomy, tooth section, extraction, cleaning and parametric data were used. For the analysis of pain data,
suturing) (1,2,8,9,17-19,21). Friedman test was used because the data are not parametric.
As soon as the procedure was finished, the volunteer For the mouth opening and trismus analyzes the two-way
immediately received the first anti-inflammatory tablet ANOVA was used since the data are parametric. Mean ±
according to the randomization (ketoprofen 100 mg b.i.d. or standard deviations were used to express the parametric
ketoprofen 200 mg + omeprazole 20 mg q.d.) and received data. Median [interquartile ranges] were used to express
a pain chart, in which he noted the exact times he took the non-parametric data. The level of significance adopted
his medication, according to the time of the end of the was 5%.
surgery. In this pain chart, the volunteer was instructed The sample size calculation was performed based on
to report any gastrointestinal adverse reaction, fill out if mouth opening, trismus, amount of rescue medication and
there was a need for ingestion of the rescue medication pain 8h after the surgery (peak) data from previously studies
(acetaminophen 750 mg), and the volunteer was instructed (8,9). The minimal effect size was 0.37741, the power was
to complete a Visual Analog Scale (0 to 100 mm) for 70% and the significance level was 5%.
postoperative pain, which contained «no pain (0 mm)»
and «worst pain possible (100 mm)». No antibiotics were Results
prescribed to the volunteers due to the pharmacological After the eligibility evaluation, the study consisted of 54
protocol applied in the present research, which corroborates volunteers; of these, two volunteers evolved with purulent
previous studies by out group (22). discharge in the postoperative period, one patient became
The parameters evaluated were as follows (Table 1): pregnant in the research development and one patient
142Braz Dent J 29(2) 2018
had different duration of both surgeries, therefore these ketoprofen 100 mg b.i.d. was 19.3 ± 5.8 min, and ketoprofen
4 volunteers they were excluded from the study with the 200 mg + omeprazole 20 mg q.d. was 21 ± 7.7, without
total sample composed of 50 volunteers. There were 33 a statistically significant difference (p = 0.0768, Table 3).
women (66%) and 17 men (34%) aged 18-38 years (mean In the postoperative pain scores documented by each
age 24 ± 5 years) (CONSORT flow chart, Fig. 1). volunteer there was a statistically significant difference
Each of the 50 volunteers completing this study had in the periods of 1.5, 7, 8, 10, 12, 16, 24, 48 and 72 h
each of the lower third molars classified as IA (n = 24), IB postoperative ketoprofen 100 mg b.i.d. and ketoprofen 200
(n = 3), IIA (n = 12), IIB (n = 9) and IIC (n = 2) according mg + omeprazole 20 mg q.d. (p0.05) (Table 4).
q.d., osteotomies and tooth sectioning were performed When analyzed for swelling and trismus values, there
in 30 surgeries, only osteotomies in 12 surgeries, and 9 was no statistically significant difference in the sum of
did not require osteotomies and tooth sectioning. For all the mean linear distances between the two drugs studied
Ketoprofen with or without omeprazole for pain
these results, no significant statistical difference was found (p>0.05). The swelling had its maximum peak significantly
regarding surgical trauma (Table 2). increased during the second day, and did not return to
The mean duration of surgery when volunteers received baseline after the seventh day for both treatments (pBraz Dent J 29(2) 2018
Regarding the maximum mouth opening, there was a present significant difference between the when volunteers
statistically significant difference (p0.05). Another parameter evaluated and that did not volunteers. In addition, no adverse reaction to the use of any
L. F. Simoneti et. al.
Figure 1: Study flowchart.
Figure 2. Visual analog scale (VAS) of self-reported postoperative pain Figure 3. Self-reported global efficacy of oral ketoprofen 100 mg
scores after lower third molar surgeries assessed at 15, 30, 45 min and b.i.d. and ketoprofen 200 mg + omeprazole 20 mg q.d. during
1, 1.5, 2, 3, 4, 5, 6, 7, 8, 10, 12, 16, 24, 48, 72 and 96 h. Scores could the seventh postoperative day as assessed using a 5-level Likert
range from 0 to 100 mm with larger scores indicating increased pain. scale (n = 50). The format of the Likert ratings was “excellent,”
Data are presented as median and interquartile range (n = 50). * Indicates “very good,” “good,” “fair,” or “poor”. * Indicates a p-value
a p-value ≤ 0.05, Wilcoxon test, for each assessed time period comparing ≤ 0.05, Wilcoxon test for the “excellent” sub-group between
ketoprofen 100 mg b.i.d. and ketoprofen 200 mg + omeprazole 20 mg q.d. research medications.
144Braz Dent J 29(2) 2018
anesthetic solution was observed by the surgeon or reported pain, swelling and trismus control, significantly better
by the volunteers during and after the surgeries. There evaluated when compared to ketoprofen 100 mg b.i.d. (p
was also no statistically significant difference regarding = 0.0001) (Fig. 3).
the time of action of the local anesthetic 4%articaine
with 1:200,000 epinephrine, number of cartridges used Discussion
in each extraction and quality of anesthesia. In addition, The present randomized and cross-over study
during all surgeries, no hypertensive peaks were observed investigated the clinical efficacy of postoperative pain
in the systolic, diastolic and mean arterial pressure data. control, swelling, and trismus using enterally ketoprofen 100
The oxygen saturation, heart rate and bleeding index did mg once every 12 h and ketoprofen 200 mg in combination
not change significantly during the surgeries (Table 3). with omeprazole 20 mg administered once every 24 h, after
There were statistically significant differences observed extractions of lower third molars under local anesthesia.
between the global evaluations of volunteers for ketoprofen As a method of evaluating acute postoperative pain, some
100 mg b.i.d. and ketoprofen 200 mg + omeprazole 20 mg researchers use analog visual scales, in which volunteers
q.d. According to the global postoperative evaluations of report the evaluation of the intensity of their pain
the volunteers, ketoprofen 200 mg + omeprazole 20 mg q.d. (1,2,8,9,23), as the present study, which used the visual
was classified as excellent and very good for postoperative analog scale to determine the intensity of postoperative
Table 2. Third molars position according to Pell & Gregory and Winter, number of surgeries without osteotomy and tooth sectioning, number of
surgeries with only osteotomy and number of surgeries with osteotomy and tooth sectioning.
Ketoprofen with or without omeprazole for pain
Ketoprofen 100 mg b.i.d. Ketoprofen 200 mg + Omeprazole 20 mg q.d.
IA 24
IB 3
IC 0
IIA 12
IIB 9
IIC 2
IIIA 0
IIIB 0
IIIC 0
Vertical 27
Horizontal 17
Distoangular 6
Mesioangular 0
Inverted 0
Buccal/Lingual Obliquity 0
Surgeries without osteotomy and tooth sectioning 9 9
Surgeries with only osteotomy 9 11
Surgeries with osteotomy and tooth sectioning 32 30
Pell and Gregory classification based on the amount of tooth covered by the anterior border of the ramus: Class I 3rd molar impaction: Situated
anterior to the anterior border of the ramus, Class II 3rd molar impaction: Crown ½ covered by the anterior border of the ramus. Class III 3rd
molar impaction: Crown fully covered by the anterior border of the ramus. The depth of the impaction relative to the adjacent tooth (A,B,or C).
Class A: the occlusal plane of the impacted tooth is at the same level as the adjacent tooth. Class B: the occlusal plane of the impacted tooth is
between the occlusal plane and the cervical line of the adjacent tooth. Class C: the occlusal plane of the impacted tooth is apical to the cervical
line of the adjacent tooth. Winter classification: Mesio-Angular: The impacted tooth is tilted toward the 2nd molar in a mesial direction. Disto-
Angular: The long axis of the 3rd molar is angled distally / posteriorly away from the 2nd molar. Horizontal: The long axis of the 3rd molar is
horizontal. Vertical: The long axis of the 3rd molar is parallel to the long axis of the 2nd molar. Buccal / Lingual Obliquity: In combination with
the above, the tooth can be buccally (tilted towards the cheek) or lingually (tilted towards the tongue) impacted. Inverted: In this position, the
tooth is displaced in an upside down position, with the crown facing the alveolar nerve.
145Braz Dent J 29(2) 2018
pain, ketoprofen 200 mg + omeprazole 20 mg q.d. had a in the present study, the results showed that ketoprofen
superior analgesic effect when compared to ketoprofen 100 100 mg presented the highest pain intensity in the 10-hour
mg b.i.d., with a statistically significant difference in the postoperative period. However, it is worth noting that for
control of pain, mainly in the periods of 1.5, 7, 8, 10, 12, 16, both drugs evaluated, pain control was satisfactory since
24, 48 and 72 h postoperative. It is worth emphasizing at the volunteers reported less than 20 mm in the visual
this moment that the acute pain control after the surgeries analog scale score, which reflects in mild pain according
by both drugs was effective, since the literature reports to Hawker et al. 2011 (23).
that pain below 45 mm does not affect the daily routine Pain, swelling and trismus arising from the extraction of
of the volunteers (17,21,24). lower third molars are usually influenced by some variables
The efficacy of ketoprofen 100 mg has also been such as time of surgery, medication, postoperative care
compared with methylprednisolone in pain control after and tissue manipulation (7). Data from the present study
third molar surgery, with peak pain intensity occurring revealed that the duration of surgery was the same when
within the first 12 h with the use of both drugs (12). volunteers were medicated either with ketoprofen 200
Although there were significant differences in pain scores mg + omeprazole 20 mg q.d. or ketoprofen 100 mg b.i.d.,
thus demonstrating the reliability
of the experimental model used
Table 3. Self-reported consumption of pain relief medication and pain scores when pain relief in the present study since the
medication was consumed volunteers were submitted to
Amount of relief Pain score Time duration, surgery to the same magnitude of surgical
Drugs
medication (tablets) (0 to 100) 1st relief medication (h) trauma.
Ketoprofen 100 mg b.i.d. 3 [4.5] 29.7 ± 20.6 7.0 [5.7] Swelling derived from third
Ketoprofen 200 mg + molar extractions presents
0.5 [3] * 27.7 ± 20.2 5.1 [5.4]
Omeprazole 20 mg q.d. maximum intensity after 48 h
L. F. Simoneti et. al.
Numbers reported with ± indicate a mean ± 1 SD, numbers reported with [ ] indicate a median and of the surgical procedure (7).
IRQ* Indicates a p-value ≤ 0.05, Wilcoxon test versus ketoprofen 100 mg b.i.d. In the present study, swelling
had its peak during the second
postoperative day as reported
Table 4. Demographic distribution and intraoperative parameters of 50 volunteers undergoing by the aforementioned study.
invasive lower third molar surgeries
After adding the linear measures
Parameters
Ketoprofen Ketoprofren 200 mg + of swelling and trismus of 48
100 mg b.i.d Omeprazole 20 mg q.d.
h and 7 days postoperatively
Age (years) 24 ± 5.0
and comparing with the
Male 17 (34%)
baseline measurement, the data
Female 33 (66%)
demonstrated that there was no
Anesthetic (cartridges) 1.5 [0] 1.5 [0] statistically significant difference
Surgery duration (min) 19.3 ± 5.8 21.0 ± 7.7 between the medications,
Onset of local anesthetic (sec) 116 ± 48 113 ± 47 which shows that there was a
Anesthesia quality (1 to 3) 1 [0] 1 [0] standardization of surgical trauma
Surgery difficulty (1 to 3) 3 [1] 3 [1] in both, and that both ketoprofen
Intraoperative bleeding (1 to 3) 1 [0] 1 [0] 100 mg b.i.d. and ketoprofen 200
Wound-healing evaluation (1 to 3) 1 [0] 1 [0] mg + omeprazole 20 mg q.d.
Preoperative period Mouth opening (mm) 47.3 ± 7.7 46.2 ± 6.7 were equalized in the control of
Mouth opening (mm) Second day 29.9 ± 8.3# 28.1 ± 7.1# postoperative swelling and trismus.
Mouth opening (mm) Seventh day 38.4 ± 8.8# 37.1 ± 9.4# Another variable widely used to
Facial measurement (mm) Preoperative period 378.5± 24.0 377.7± 21.4 predict the difficulty of extracting
Facial swelling (mm) Second day 398.1 ± 23.2# 394.6 ± 21.9# the lower third molars, and
Facial swelling (mm) Seventh day 386.1 ± 23.8# 383.8 ± 22.4# influences the level of surgical
Body temperature (oC) Preoperative period 36.02 ± 0.77 36.06 ± 0.17 trauma, is the Pell and Gregory (9)
Body temperature (oC) Second day 36.09 ± 0.55 36.36 ± 1.10 classification based on their spatial
Body temperature ( C) Seventh day
o 35.57 ± 0.50 36.00 ± 0 relationships with the ascending
Numbers reported with ± indicate a mean ± 1 SD, numbers reported with [ ] indicate a median mandible branch and the occlusal
and IRQ. * versus ketoprofen 100 mg b.i.d. and # versus preoperative period. plane (16). In the present study,
146Braz Dent J 29(2) 2018
although most of the lower third molars were classified which NSAIDs present the highest risk of gastrointestinal
as IA (n = 24) according to Pell and Gregory and in the complications. In a meta-analysis performed to assess the
vertical position (n = 27) according to Winter (16), there risk of severe gastrointestinal complications associated
was a high level of surgical difficulty, since there was a with 12 commonly used chronic NSAIDs, ibuprofen
need for osteotomy and tooth sectioning in the great represented the lowest risk of gastrointestinal toxicity. In
majority of dental elements due to root dilaceration and contrast, the relative risk (RR) of some NSAIDs compared
divergence, besides the degree of impaction, culminating with ibuprofen (RR = 1) reached values of up to 3.8
with greater surgical trauma and, consequently, an increase (piroxicam) and 4.2 (ketoprofen) (28). Ketoprofen 200 mg
in postoperative swelling and trismus. drug in combination with omeprazole 20 mg is new on the
The clinical efficacy of ketoprofen in the control market and is indicated for the symptomatic treatment
of postoperative pain after extractions of third molars of rheumatoid arthritis and osteoarthritis in volunteers
has been widely described in clinical trials (5, 25). The at risk of developing ulcer or erosions in the stomach,
use of ketoprofen 75 mg and acetaminophen 1,000 mg duodenum or other part of the intestine with the use
was compared, showing lower levels of pain reported by of NSAIDs. One study evaluated whether the effect of
volunteers who received ketoprofen, thus demonstrating a dose of omeprazole would alter the pharmacokinetics
that even at lower doses ketoprofen is effective in the of enteric ketoprofen and determined that omeprazole
control of postoperative pain (25). does not affect hepatic flow rate and is also a more
Another parameter used to define the postoperative direct agent for the inhibition of gastric acid production,
pain intensity of the volunteers in the present study was offering advantages for the study of the effect of gastric
the amount of rescue analgesic medication (acetaminophen acidity on the release of enteric coated products (29). The
Ketoprofen with or without omeprazole for pain
750 mg) used which corroborate with many studies pharmacokinetic profiles of ketoprofen and omeprazole
evaluating the patient’s need to use pain relief medication, components in this combination used in the present study
thus demonstrating the drug’s efficacy in pain modulation are comparable to those of the separately administered
(4, 9). When volunteers took ketoprofen 100 mg b.i.d., they ketoprofen and omeprazole components. There is no
consumed a greater amount of rescue analgesic medication influence on the pharmacokinetics of ketoprofen when
compared to the use of ketoprofen of 200 mg + omeprazole administered concomitantly with omeprazole (13-15,28).
20 mg q.d. (p=0.0026) to reduce postoperative pain. The Following administration of both study drugs, no
mean time in hours for the volunteers to take the first tablet adverse reactions were reported by the volunteers. This
of rescue analgesic medication, the results show that when may be due to the fact that the NSAIDs administered were
they took ketoprofen 200 mg + omeprazole 20 mg q.d. was for a short period of time, and volunteers did not have
5 h, whereas 7 h when they used ketoprofen 100 mg b.i.d. any underlying disease, blood dyscrasias or drug allergy.
(p=0.53). The results differ of Pouchain et al. 2015 (26) Based on the assumption that other methods for pain
compared the effect of nimesulide 100 mg and ketoprofen assessment contribute to research adopting this type of
100 mg, both b.i.d., on the inflammatory parameters related study model such as in the present study, global assessment
to the surgical removal of third molars, both administered is a widely used tool offering a holistic view of drug efficacy
immediately after the surgical procedure, but the use of in general patient conception (2, 8, 9, 18). Therefore,
pain relief drugs was considered unnecessary by volunteer. ketoprofen 200 mg + omeprazole 20 mg b.i.d. shows lower
The data showed that although complete pain relief was levels of postoperative pain in comparison to ketoprofen
not observed, the level of pain was tolerable to volunteers. 100 mg b.i.d., thus receiving an excellent classification in
In contrast, the administration of several NSAIDs, the global evaluation of the volunteers participating in
including ketoprofen, was evaluated in volunteers this study. As described, the combination of ketoprofen
undergoing surgery for extraction of impacted third 200 mg + omeprazole 20 mg includes a prolonged release
molars and it was observed that 75% of the volunteers form of ketoprofen and a gastroresistant release form of
consumed pain relief medication during the early onset of omeprazole, both suitable for once-daily dosing (15). In
pain (3 h after the surgical procedure) and that 24% of the addition, in comparison with other studies by our study
volunteers consumed pain relief medication immediately group evaluating different NSAIDs in bilateral third molar
after the surgical procedure (27). In the present study, when extraction model, ketoprofen 200 mg + omeprazole 20 mg
volunteers took ketoprofen 100 mg b.i.d., used significantly b.i.d. showed as good pain control as other drugs evaluated
higher total amount of rescue analgesic medication such as piroxicam, valdecoxib, etoricoxib, meloxicam,
compared to when took ketoprofen 200 mg + omeprazole ketorolac, naproxen (1, 2, 8, 9, 21).
20 mg b.i.d. (76 vs. 50% respectively, p=0.001). In summary, the results of the present study revealed
It is particularly important for the clinician to know that when volunteers took ketoprofen 200 mg + omeprazole
147Braz Dent J 29(2) 2018
nonsteroidal anti-inflammatory drugs, ibuprofen and flurbiprofen,
20 mg (q.d.), they reported significantly less postoperative with methylprednisolone and placebo for acute pain, swelling, and
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mg (b.i.d.). In addition, self-reported global efficacy was third molar extractions: A double blinded crossover study. Med Oral
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omeprazole 20 mg (q.d.). As far as swelling and trismus TJ, Brozoski DT, et al. Efficacy of oral diclofenac with or without codeine
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Em vista dos problemas gastrointestinais gerados pelo uso do cetoprofeno, molar surgery. A prospective, randomized, double-blinded clinical trial.
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No entanto, esta eficácia de associação no controle da dor aguda não 11. Orozco-Solis M, Garcia-Avalos Y, Pichardo-Ramirez C, Tobias-Azua
foi estabelecida. A extração bilateral de terceiros molares inferiores F, Zapata-Morales JR, Aragon-Martinez OH, et al. Single dose of
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Financial support by São Paulo Research Foundation (FAPESP)
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2014/25792-0.
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Ketoprofen with or without omeprazole for pain
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